Search results for: computational fluid dynamics "CFD"
100 In Silico Modeling of Drugs Milk/Plasma Ratio in Human Breast Milk Using Structures Descriptors
Authors: Navid Kaboudi, Ali Shayanfar
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Introduction: Feeding infants with safe milk from the beginning of their life is an important issue. Drugs which are used by mothers can affect the composition of milk in a way that is not only unsuitable, but also toxic for infants. Consuming permeable drugs during that sensitive period by mother could lead to serious side effects to the infant. Due to the ethical restrictions of drug testing on humans, especially women, during their lactation period, computational approaches based on structural parameters could be useful. The aim of this study is to develop mechanistic models to predict the M/P ratio of drugs during breastfeeding period based on their structural descriptors. Methods: Two hundred and nine different chemicals with their M/P ratio were used in this study. All drugs were categorized into two groups based on their M/P value as Malone classification: 1: Drugs with M/P>1, which are considered as high risk 2: Drugs with M/P>1, which are considered as low risk Thirty eight chemical descriptors were calculated by ACD/labs 6.00 and Data warrior software in order to assess the penetration during breastfeeding period. Later on, four specific models based on the number of hydrogen bond acceptors, polar surface area, total surface area, and number of acidic oxygen were established for the prediction. The mentioned descriptors can predict the penetration with an acceptable accuracy. For the remaining compounds (N= 147, 158, 160, and 174 for models 1 to 4, respectively) of each model binary regression with SPSS 21 was done in order to give us a model to predict the penetration ratio of compounds. Only structural descriptors with p-value<0.1 remained in the final model. Results and discussion: Four different models based on the number of hydrogen bond acceptors, polar surface area, and total surface area were obtained in order to predict the penetration of drugs into human milk during breastfeeding period About 3-4% of milk consists of lipids, and the amount of lipid after parturition increases. Lipid soluble drugs diffuse alongside with fats from plasma to mammary glands. lipophilicity plays a vital role in predicting the penetration class of drugs during lactation period. It was shown in the logistic regression models that compounds with number of hydrogen bond acceptors, PSA and TSA above 5, 90 and 25 respectively, are less permeable to milk because they are less soluble in the amount of fats in milk. The pH of milk is acidic and due to that, basic compounds tend to be concentrated in milk than plasma while acidic compounds may consist lower concentrations in milk than plasma. Conclusion: In this study, we developed four regression-based models to predict the penetration class of drugs during the lactation period. The obtained models can lead to a higher speed in drug development process, saving energy, and costs. Milk/plasma ratio assessment of drugs requires multiple steps of animal testing, which has its own ethical issues. QSAR modeling could help scientist to reduce the amount of animal testing, and our models are also eligible to do that.Keywords: logistic regression, breastfeeding, descriptors, penetration
Procedia PDF Downloads 7199 Contextual Toxicity Detection with Data Augmentation
Authors: Julia Ive, Lucia Specia
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Understanding and detecting toxicity is an important problem to support safer human interactions online. Our work focuses on the important problem of contextual toxicity detection, where automated classifiers are tasked with determining whether a short textual segment (usually a sentence) is toxic within its conversational context. We use “toxicity” as an umbrella term to denote a number of variants commonly named in the literature, including hate, abuse, offence, among others. Detecting toxicity in context is a non-trivial problem and has been addressed by very few previous studies. These previous studies have analysed the influence of conversational context in human perception of toxicity in controlled experiments and concluded that humans rarely change their judgements in the presence of context. They have also evaluated contextual detection models based on state-of-the-art Deep Learning and Natural Language Processing (NLP) techniques. Counterintuitively, they reached the general conclusion that computational models tend to suffer performance degradation in the presence of context. We challenge these empirical observations by devising better contextual predictive models that also rely on NLP data augmentation techniques to create larger and better data. In our study, we start by further analysing the human perception of toxicity in conversational data (i.e., tweets), in the absence versus presence of context, in this case, previous tweets in the same conversational thread. We observed that the conclusions of previous work on human perception are mainly due to data issues: The contextual data available does not provide sufficient evidence that context is indeed important (even for humans). The data problem is common in current toxicity datasets: cases labelled as toxic are either obviously toxic (i.e., overt toxicity with swear, racist, etc. words), and thus context does is not needed for a decision, or are ambiguous, vague or unclear even in the presence of context; in addition, the data contains labeling inconsistencies. To address this problem, we propose to automatically generate contextual samples where toxicity is not obvious (i.e., covert cases) without context or where different contexts can lead to different toxicity judgements for the same tweet. We generate toxic and non-toxic utterances conditioned on the context or on target tweets using a range of techniques for controlled text generation(e.g., Generative Adversarial Networks and steering techniques). On the contextual detection models, we posit that their poor performance is due to limitations on both of the data they are trained on (same problems stated above) and the architectures they use, which are not able to leverage context in effective ways. To improve on that, we propose text classification architectures that take the hierarchy of conversational utterances into account. In experiments benchmarking ours against previous models on existing and automatically generated data, we show that both data and architectural choices are very important. Our model achieves substantial performance improvements as compared to the baselines that are non-contextual or contextual but agnostic of the conversation structure.Keywords: contextual toxicity detection, data augmentation, hierarchical text classification models, natural language processing
Procedia PDF Downloads 17098 Polyurethane Membrane Mechanical Property Study for a Novel Carotid Covered Stent
Authors: Keping Zuo, Jia Yin Chia, Gideon Praveen Kumar Vijayakumar, Foad Kabinejadian, Fangsen Cui, Pei Ho, Hwa Liang Leo
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Carotid artery is the major vessel supplying blood to the brain. Carotid artery stenosis is one of the three major causes of stroke and the stroke is the fourth leading cause of death and the first leading cause of disability in most developed countries. Although there is an increasing interest in carotid artery stenting for treatment of cervical carotid artery bifurcation therosclerotic disease, currently available bare metal stents cannot provide an adequate protection against the detachment of the plaque fragments over diseased carotid artery, which could result in the formation of micro-emboli and subsequent stroke. Our research group has recently developed a novel preferential covered-stent for carotid artery aims to prevent friable fragments of atherosclerotic plaques from flowing into the cerebral circulation, and yet retaining the ability to preserve the flow of the external carotid artery. The preliminary animal studies have demonstrated the potential of this novel covered-stent design for the treatment of carotid therosclerotic stenosis. The purpose of this study is to evaluate the biomechanical property of PU membrane of different concentration configurations in order to refine the stent coating technique and enhance the clinical performance of our novel carotid covered stent. Results from this study also provide necessary material property information crucial for accurate simulation analysis for our stents. Method: Medical grade Polyurethane (ChronoFlex AR) was used to prepare PU membrane specimens. Different PU membrane configurations were subjected to uniaxial test: 22%, 16%, and 11% PU solution were made by mixing the original solution with proper amount of the Dimethylacetamide (DMAC). The specimens were then immersed in physiological saline solution for 24 hours before test. All specimens were moistened with saline solution before mounting and subsequent uniaxial testing. The specimens were preconditioned by loading the PU membrane sample to a peak stress of 5.5 Mpa for 10 consecutive cycles at a rate of 50 mm/min. The specimens were then stretched to failure at the same loading rate. Result: The results showed that the stress-strain response curves of all PU membrane samples exhibited nonlinear characteristic. For the ultimate failure stress, 22% PU membrane was significantly higher than 16% (p<0.05). In general, our preliminary results showed that lower concentration PU membrane is stiffer than the higher concentration one. From the perspective of mechanical properties, 22% PU membrane is a better choice for the covered stent. Interestingly, the hyperelastic Ogden model is able to accurately capture the nonlinear, isotropic stress-strain behavior of PU membrane with R2 of 0.9977 ± 0.00172. This result will be useful for future biomechanical analysis of our stent designs and will play an important role for computational modeling of our covered stent fatigue study.Keywords: carotid artery, covered stent, nonlinear, hyperelastic, stress, strain
Procedia PDF Downloads 31097 A Foucauldian Analysis of Postcolonial Hybridity in a Kuwaiti Novel
Authors: Annette Louise Dupont
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Background and Introduction: Broadly defined, hybridity is a condition of racial and cultural ‘cross-pollination’ which arises as a result of contact between colonized and colonizer. It remains a highly contested concept in postcolonial studies as it is implicitly underpinned by colonial notions of ‘racial purity.’ While some postcolonial scholars argue that individuals exercise significant agency in the construction of their hybrid subjectivities, others underscore associated experiences of exclusion, marginalization, and alienation. Kuwait and the Philippines are among the most disparate of contemporary postcolonial states. While oil resources transformed the former British Mandate of Kuwait into one of the world’s richest countries, enduring poverty in the former US colony of the Philippines drives a global diaspora which produces multiple Filipino hybridities. Although more Filipinos work in the Arabian Gulf than in any other region of the world, scholarly and literary accounts of their experiences of hybridization in this region are relatively scarce when compared to those set in North America, Australia, Asia, and Europe. Study Aims and Significance: This paper aims to address this existing lacuna by investigating hybridity and other postcolonial themes in a novel by a Kuwaiti author which vividly portrays the lives of immigrants and citizens in Kuwait and which gives a rare voice and insight into the struggles of an Arab-Filipino and European-Filipina. Specifically, this paper explores the relationships between colonial discourses of ‘black’ and ‘white’ and postcolonial discourses pertaining to ‘brown’ Filipinos and ‘brown’ Arabs, in order to assess their impacts on the protagonists’ hybrid subjectivities. Methodology: Foucault’s notions of discourse not only provide a conceptual basis for analyzing the colonial ideology of Orientalism, but his theories related to the social exclusion of the ‘mad’ also elucidate the mechanisms by which power can operate to marginalize, alienate and subjectify the Other, therefore a Foucauldian lens is applied to the analysis of postcolonial themes and hybrid subjectivities portrayed in the novel. Findings: The study finds that Kuwaiti and Filipino discursive practices mirror those of former white colonialists and colonized black laborers and that these discursive practices combine with a former British colonial system of foreign labor sponsorship to create a form of governmentality in Kuwait which is based on exclusion and control. The novel’s rich social description and the reflections of the key protagonist and narrator suggest that such fiction has a significant role to play in highlighting the historical and cultural specificities of experiences of postcolonial hybridity in under-researched geographic, economic, social, and political settings. Whereas hybridity can appear abstract in scholarly accounts, the significance of literary accounts in which the lived experiences of hybrid protagonists are anchored to specific historical periods, places and discourses, is that contextual particularities are neither obscured nor dehistoricized. Conclusions: The application of Foucauldian theorizations of discourse, disciplinary, and biopower to the analysis of this Kuwaiti literary text serves to extend an understanding of the effects of contextually-specific discourses on hybrid Filipino subjectivities, as well as a knowledge of prevailing social dynamics in a little-researched postcolonial Arabian Gulf state.Keywords: Filipino, Foucault, hybridity, Kuwait
Procedia PDF Downloads 12896 Evaluation of Coupled CFD-FEA Simulation for Fire Determination
Authors: Daniel Martin Fellows, Sean P. Walton, Jennifer Thompson, Oubay Hassan, Ella Quigley, Kevin Tinkham
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Fire performance is a crucial aspect to consider when designing cladding products, and testing this performance is extremely expensive. Appropriate use of numerical simulation of fire performance has the potential to reduce the total number of fire tests required when designing a product by eliminating poor-performing design ideas early in the design phase. Due to the complexity of fire and the large spectrum of failures it can cause, multi-disciplinary models are needed to capture the complex fire behavior and its structural effects on its surroundings. Working alongside Tata Steel U.K., the authors have focused on completing a coupled CFD-FEA simulation model suited to test Polyisocyanurate (PIR) based sandwich panel products to gain confidence before costly experimental standards testing. The sandwich panels are part of a thermally insulating façade system primarily for large non-domestic buildings. The work presented in this paper compares two coupling methodologies of a replicated physical experimental standards test LPS 1181-1, carried out by Tata Steel U.K. The two coupling methodologies that are considered within this research are; one-way and two-way. A one-way coupled analysis consists of importing thermal data from the CFD solver into the FEA solver. A two-way coupling analysis consists of continuously importing the updated changes in thermal data, due to the fire's behavior, to the FEA solver throughout the simulation. Likewise, the mechanical changes will also be updated back to the CFD solver to include geometric changes within the solution. For CFD calculations, a solver called Fire Dynamic Simulator (FDS) has been chosen due to its adapted numerical scheme to focus solely on fire problems. Validation of FDS applicability has been achieved in past benchmark cases. In addition, an FEA solver called ABAQUS has been chosen to model the structural response to the fire due to its crushable foam plasticity model, which can accurately model the compressibility of PIR foam. An open-source code called FDS-2-ABAQUS is used to couple the two solvers together, using several python modules to complete the process, including failure checks. The coupling methodologies and experimental data acquired from Tata Steel U.K are compared using several variables. The comparison data includes; gas temperatures, surface temperatures, and mechanical deformation of the panels. Conclusions are drawn, noting improvements to be made on the current coupling open-source code FDS-2-ABAQUS to make it more applicable to Tata Steel U.K sandwich panel products. Future directions for reducing the computational cost of the simulation are also considered.Keywords: fire engineering, numerical coupling, sandwich panels, thermo fluids
Procedia PDF Downloads 8995 Assessment of DNA Sequence Encoding Techniques for Machine Learning Algorithms Using a Universal Bacterial Marker
Authors: Diego Santibañez Oyarce, Fernanda Bravo Cornejo, Camilo Cerda Sarabia, Belén Díaz Díaz, Esteban Gómez Terán, Hugo Osses Prado, Raúl Caulier-Cisterna, Jorge Vergara-Quezada, Ana Moya-Beltrán
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The advent of high-throughput sequencing technologies has revolutionized genomics, generating vast amounts of genetic data that challenge traditional bioinformatics methods. Machine learning addresses these challenges by leveraging computational power to identify patterns and extract information from large datasets. However, biological sequence data, being symbolic and non-numeric, must be converted into numerical formats for machine learning algorithms to process effectively. So far, some encoding methods, such as one-hot encoding or k-mers, have been explored. This work proposes additional approaches for encoding DNA sequences in order to compare them with existing techniques and determine if they can provide improvements or if current methods offer superior results. Data from the 16S rRNA gene, a universal marker, was used to analyze eight bacterial groups that are significant in the pulmonary environment and have clinical implications. The bacterial genes included in this analysis are Prevotella, Abiotrophia, Acidovorax, Streptococcus, Neisseria, Veillonella, Mycobacterium, and Megasphaera. These data were downloaded from the NCBI database in Genbank file format, followed by a syntactic analysis to selectively extract relevant information from each file. For data encoding, a sequence normalization process was carried out as the first step. From approximately 22,000 initial data points, a subset was generated for testing purposes. Specifically, 55 sequences from each bacterial group met the length criteria, resulting in an initial sample of approximately 440 sequences. The sequences were encoded using different methods, including one-hot encoding, k-mers, Fourier transform, and Wavelet transform. Various machine learning algorithms, such as support vector machines, random forests, and neural networks, were trained to evaluate these encoding methods. The performance of these models was assessed using multiple metrics, including the confusion matrix, ROC curve, and F1 Score, providing a comprehensive evaluation of their classification capabilities. The results show that accuracies between encoding methods vary by up to approximately 15%, with the Fourier transform obtaining the best results for the evaluated machine learning algorithms. These findings, supported by the detailed analysis using the confusion matrix, ROC curve, and F1 Score, provide valuable insights into the effectiveness of different encoding methods and machine learning algorithms for genomic data analysis, potentially improving the accuracy and efficiency of bacterial classification and related genomic studies.Keywords: DNA encoding, machine learning, Fourier transform, Fourier transformation
Procedia PDF Downloads 2394 Pulmonary Complication of Chronic Liver Disease and the Challenges Identifying and Managing Three Patients
Authors: Aidan Ryan, Nahima Miah, Sahaj Kaur, Imogen Sutherland, Mohamed Saleh
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Pulmonary symptoms are a common presentation to the emergency department. Due to a lack of understanding of the underlying pathophysiology, chronic liver disease is not often considered a cause of dyspnea. We present three patients who were admitted with significant respiratory distress secondary to hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. The first is a 27-year-old male with a 6-month history of progressive dyspnea. The patient developed a severe type 1 respiratory failure with a PaO₂ of 6.3kPa and was escalated to critical care, where he was managed with non-invasive ventilation to maintain oxygen saturation. He had an agitated saline contrast echocardiogram, which showed the presence of a possible shunt. A CT angiogram revealed significant liver cirrhosis, portal hypertension, and large para esophageal varices. Ultrasound of the abdomen showed coarse liver echo patter and enlarged spleen. Along with these imaging findings, his biochemistry demonstrated impaired synthetic liver function with an elevated international normalized ratio (INR) of 1.4 and hypoalbuminaemia of 28g/L. The patient was then transferred to a tertiary center for further management. Further investigations confirmed a shunt of 56%, and liver biopsy confirmed cirrhosis suggestive of alpha-1-antitripsyin deficiency. The findings were consistent with a diagnosis of hepatopulmonary syndrome, and the patient is awaiting a liver transplant. The second patient is a 56-year-old male with a 12-month history of worsening dyspnoea, jaundice, confusion. His medical history included liver cirrhosis, portal hypertension, and grade 1 oesophageal varices secondary to significant alcohol excess. On admission, he developed a type 1 respiratory failure with PaO₂ of 6.8kPa requiring 10L of oxygen. CT pulmonary angiogram was negative for pulmonary embolism but showed evidence of chronic pulmonary hypertension, liver cirrhosis, and portal hypertension. An echocardiogram revealed a grossly dilated right heart with reduced function, pulmonary and tricuspid regurgitation, and pulmonary artery pressures estimated at 78mmHg. His biochemical markers showed impaired synthetic liver function with an INR of 3.2, albumin of 29g/L, along with raised bilirubin of 148mg/dL. During his long admission, he was managed with diuretics with little improvement. After three weeks, he was diagnosed with portopulmonary hypertension and was commenced on terlipressin. This resulted in successfully weaning off oxygen, and he was discharged home. The third patient is a 61-year-old male who presented to the local ambulatory care unit for therapeutic paracentesis on a background of decompensated liver cirrhosis. On presenting, he complained of a 2-day history of worsening dyspnoea and a productive cough. Chest x-ray showed a large pleural effusion, increasing in size over the previous eight months, and his abdomen was visibly distended with ascitic fluid. Unfortunately, the patient deteriorated, developing a larger effusion along with an increase in oxygen demand, and passed away. Without underlying cardiorespiratory disease, in the presence of a persistent pleural effusion with underlying decompensated cirrhosis, he was diagnosed with hepatic hydrothorax. While each presented with dyspnoea, the cause and underlying pathophysiology differ significantly from case to case. By describing these complications, we hope to improve awareness and aid prompt and accurate diagnosis, vital for improving outcomes.Keywords: dyspnea, hepatic hydrothorax, hepatopulmonary syndrome, portopulmonary syndrome
Procedia PDF Downloads 12193 Steel Concrete Composite Bridge: Modelling Approach and Analysis
Authors: Kaviyarasan D., Satish Kumar S. R.
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India being vast in area and population with great scope of international business, roadways and railways network connection within the country is expected to have a big growth. There are numerous rail-cum-road bridges constructed across many major rivers in India and few are getting very old. So there is more possibility of repairing or coming up with such new bridges in India. Analysis and design of such bridges are practiced through conventional procedure and end up with heavy and uneconomical sections. Such heavy class steel bridges when subjected to high seismic shaking has more chance to fail by stability because the members are too much rigid and stocky rather than being flexible to dissipate the energy. This work is the collective study of the researches done in the truss bridge and steel concrete composite truss bridges presenting the method of analysis, tools for numerical and analytical modeling which evaluates its seismic behaviour and collapse mechanisms. To ascertain the inelastic and nonlinear behaviour of the structure, generally at research level static pushover analysis is adopted. Though the static pushover analysis is now extensively used for the framed steel and concrete buildings to study its lateral action behaviour, those findings by pushover analysis done for the buildings cannot directly be used for the bridges as such, because the bridges have completely a different performance requirement, behaviour and typology as compared to that of the buildings. Long span steel bridges are mostly the truss bridges. Truss bridges being formed by many members and connections, the failure of the system does not happen suddenly with single event or failure of one member. Failure usually initiates from one member and progresses gradually to the next member and so on when subjected to further loading. This kind of progressive collapse of the truss bridge structure is dependent on many factors, in which the live load distribution and span to length ratio are most significant. The ultimate collapse is anyhow by the buckling of the compression members only. For regular bridges, single step pushover analysis gives results closer to that of the non-linear dynamic analysis. But for a complicated bridge like heavy class steel bridge or the skewed bridges or complicated dynamic behaviour bridges, nonlinear analysis capturing the progressive yielding and collapse pattern is mandatory. With the knowledge of the postelastic behaviour of the bridge and advancements in the computational facility, the current level of analysis and design of bridges has moved to state of ascertaining the performance levels of the bridges based on the damage caused by seismic shaking. This is because the buildings performance levels deals much with the life safety and collapse prevention levels, whereas the bridges mostly deal with the extent damages and how quick it can be repaired with or without disturbing the traffic after a strong earthquake event. The paper would compile the wide spectrum of modeling to analysis of the steel concrete composite truss bridges in general.Keywords: bridge engineering, performance based design of steel truss bridge, seismic design of composite bridge, steel-concrete composite bridge
Procedia PDF Downloads 18592 Two Houses in the Arabian Desert: Assessing the Built Work of RCR Architects in the UAE
Authors: Igor Peraza Curiel, Suzanne Strum
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Today, when many foreign architects are receiving commissions in the United Arab Emirates, it is essential to analyze how their designs are influenced by the region's culture, environment, and building traditions. This study examines the approach to siting, geometry, construction methods, and material choices in two private homes for a family in Dubai, a project being constructed on adjacent sites by the acclaimed Spanish team of RCR Architects. Their third project in Dubai, the houses mark a turning point in their design approach to the desert. The Pritzker Prize-winning architects of RCR gained renown for building works deeply responsive to the history, landscape, and customs of their hometown in a volcanic area of the Catalonia region of Spain. Key formative projects and their entry to practice in UAE will be analyzed according to the concepts of place identity, the poetics of construction, and material imagination. The poetics of construction, a theoretical position with a long practical tradition, was revived by the British critic Kenneth Frampton. The idea of architecture as a constructional craft is related to the concepts of material imagination and place identity--phenomenological concerns with the creative engagement with local matter and topography that are at the very essence of RCR's way of designing, detailing, and making. Our study situates RCR within the challenges of building in the region, where western forms and means have largely replaced the ingenious responsiveness of indigenous architecture to the climate and material scarcity. The dwellings, iterations of the same steel and concrete vaulting system, highlight the conceptual framework of RCR's design approach to offer a study in contemporary critical regionalism. The Kama House evokes Bedouin tents, while the Alwah House takes the form of desert dunes in response to the temporality of the winds. Metal mesh screens designed to capture the shifting sands will complete the forms. The original research draws on interviews with the architects and unique documentation provided by them and collected by the authors during on-site visits. By examining the two houses in-depth, this paper foregrounds a series of timely questions: 1) What is the impact of the local climatic, cultural, and material conditions on their project in the UAE? 2) How does this work further their experiences in the region? 3) How has RCR adapted their construction techniques as their work expands beyond familiar settings? The investigation seeks to understand how the design methodology developed for more than 20 years and enmeshed in the regional milieu of their hometown can transform as the architects encounter unique characteristics and values in the Middle East. By focusing on the contemporary interpretation of Arabic geometry and elements, the houses reveal the role of geometry, tectonics, and material specificity in the realization from conceptual sketches to built form. In emphasizing the importance of regional responsiveness, the dynamics of international construction practice, and detailing this study highlights essential issues for professionals and students looking to practice in an increasingly global market.Keywords: material imagination, regional responsiveness, place identity, poetics of construction
Procedia PDF Downloads 14591 Synthesis, Computational Studies, Antioxidant and Anti-Inflammatory Bio-Evaluation of 2,5-Disubstituted- 1,3,4-Oxadiazole Derivatives
Authors: Sibghat Mansoor Rana, Muhammad Islam, Hamid Saeed, Hummera Rafique, Muhammad Majid, Muhammad Tahir Aqeel, Fariha Imtiaz, Zaman Ashraf
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The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flur- biprofen moiety with the aim to explore the potential of target molecules to decrease the oxidative stress. The title compounds Ox-6a-f were prepared by simple reactions in which a flurbiprofen –COOH group was esterified with methanol in an acid-catalyzed medium, which was then reacted with hydrazine to afford the corresponding hydrazide. The acid hydrazide was then cyclized into 1,3,4-oxadiazole-2-thiol by reacting with CS2 in the presence of KOH. The title compounds Ox-6a-f were synthesized by the reaction of an –SH group with various alkyl/aryl chlorides, which involves an S-alkylation reaction. The structures of the synthesized Ox-6a-f derivatives were ascer- tained by spectroscopic data. The in silico molecular docking was performed against target proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 (PDBID 6Y3C) to determine the binding affinity of the synthesized compounds with these structures. It has been inferred that most of the synthesized compounds bind well with an active binding site of 5KIR compared to 6Y3C, and especially compound Ox-6f showed excellent binding affinity (7.70 kcal/mol) among all synthesized compounds Ox-6a-f. The molecular dynamic (MD) simulation has also been performed to check the stability of docking complexes of ligands with COX-2 by determining their root mean square deviation and root mean square fluctuation. Little fluctuation was observed in case of Ox-6f, which forms the most stable complex with COX-2. The comprehensive antioxidant potential of the synthesized compounds has been evaluated by determining their free radical scavenging activity, including DPPH, OH, nitric oxide (NO), and iron chelation assay. The derivative Ox-6f showed promising results with 80.23% radical scavenging potential at a dose of 100 μg/mL while ascorbic acid exhibited 87.72% inhibition at the same dose. The anti-inflammatory activity of the final products has also been performed, and inflammatory markers were assayed, such as a thiobarbituric acid-reducing substance, nitric oxide, interleukin-6 (IL-6), and COX-2. The derivatives Ox-6d and Ox-6f displayed higher anti-inflammatory activity, exhibiting 70.56% and 74.16% activity, respectively. The results were compared with standard ibuprofen, which showed 84.31% activity at the same dose, 200 μg/mL. The anti-inflammatory potential has been performed by following the carrageen-induced hind paw edema model, and results showed that derivative Ox-6f exhibited 79.83% reduction in edema volume compared to standard ibuprofen, which reduced 84.31% edema volume. As dry lab and wet lab results confirm each other, it has been deduced that derivative Ox-6f may serve as the lead structure to design potent compounds to address oxidative stress.Keywords: synthetic chemistry, pharmaceutical chemistry, oxadiazole derivatives, anti-inflammatory, anti-cancer compounds
Procedia PDF Downloads 1590 Text Mining Past Medical History in Electrophysiological Studies
Authors: Roni Ramon-Gonen, Amir Dori, Shahar Shelly
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Background and objectives: Healthcare professionals produce abundant textual information in their daily clinical practice. The extraction of insights from all the gathered information, mainly unstructured and lacking in normalization, is one of the major challenges in computational medicine. In this respect, text mining assembles different techniques to derive valuable insights from unstructured textual data, so it has led to being especially relevant in Medicine. Neurological patient’s history allows the clinician to define the patient’s symptoms and along with the result of the nerve conduction study (NCS) and electromyography (EMG) test, assists in formulating a differential diagnosis. Past medical history (PMH) helps to direct the latter. In this study, we aimed to identify relevant PMH, understand which PMHs are common among patients in the referral cohort and documented by the medical staff, and examine the differences by sex and age in a large cohort based on textual format notes. Methods: We retrospectively identified all patients with abnormal NCS between May 2016 to February 2022. Age, gender, and all NCS attributes reports were recorded, including the summary text. All patients’ histories were extracted from the text report by a query. Basic text cleansing and data preparation were performed, as well as lemmatization. Very popular words (like ‘left’ and ‘right’) were deleted. Several words were replaced with their abbreviations. A bag of words approach was used to perform the analyses. Different visualizations which are common in text analysis, were created to easily grasp the results. Results: We identified 5282 unique patients. Three thousand and five (57%) patients had documented PMH. Of which 60.4% (n=1817) were males. The total median age was 62 years (range 0.12 – 97.2 years), and the majority of patients (83%) presented after the age of forty years. The top two documented medical histories were diabetes mellitus (DM) and surgery. DM was observed in 16.3% of the patients, and surgery at 15.4%. Other frequent patient histories (among the top 20) were fracture, cancer (ca), motor vehicle accident (MVA), leg, lumbar, discopathy, back and carpal tunnel release (CTR). When separating the data by sex, we can see that DM and MVA are more frequent among males, while cancer and CTR are less frequent. On the other hand, the top medical history in females was surgery and, after that, DM. Other frequent histories among females are breast cancer, fractures, and CTR. In the younger population (ages 18 to 26), the frequent PMH were surgery, fractures, trauma, and MVA. Discussion: By applying text mining approaches to unstructured data, we were able to better understand which medical histories are more relevant in these circumstances and, in addition, gain additional insights regarding sex and age differences. These insights might help to collect epidemiological demographical data as well as raise new hypotheses. One limitation of this work is that each clinician might use different words or abbreviations to describe the same condition, and therefore using a coding system can be beneficial.Keywords: abnormal studies, healthcare analytics, medical history, nerve conduction studies, text mining, textual analysis
Procedia PDF Downloads 9689 Unveiling the Dynamics of Preservice Teachers’ Engagement with Mathematical Modeling through Model Eliciting Activities: A Comprehensive Exploration of Acceptance and Resistance Towards Modeling and Its Pedagogy
Authors: Ozgul Kartal, Wade Tillett, Lyn D. English
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Despite its global significance in curricula, mathematical modeling encounters persistent disparities in recognition and emphasis within regular mathematics classrooms and teacher education across countries with diverse educational and cultural traditions, including variations in the perceived role of mathematical modeling. Over the past two decades, increased attention has been given to the integration of mathematical modeling into national curriculum standards in the U.S. and other countries. Therefore, the mathematics education research community has dedicated significant efforts to investigate various aspects associated with the teaching and learning of mathematical modeling, primarily focusing on exploring the applicability of modeling in schools and assessing students', teachers', and preservice teachers' (PTs) competencies and engagement in modeling cycles and processes. However, limited attention has been directed toward examining potential resistance hindering teachers and PTs from effectively implementing mathematical modeling. This study focuses on how PTs, without prior modeling experience, resist and/or embrace mathematical modeling and its pedagogy as they learn about models and modeling perspectives, navigate the modeling process, design and implement their modeling activities and lesson plans, and experience the pedagogy enabling modeling. Model eliciting activities (MEAs) were employed due to their high potential to support the development of mathematical modeling pedagogy. The mathematical modeling module was integrated into a mathematics methods course to explore how PTs embraced or resisted mathematical modeling and its pedagogy. The module design included reading, reflecting, engaging in modeling, assessing models, creating a modeling task (MEA), and designing a modeling lesson employing an MEA. Twelve senior undergraduate students participated, and data collection involved video recordings, written prompts, lesson plans, and reflections. An open coding analysis revealed acceptance and resistance toward teaching mathematical modeling. The study identified four overarching themes, including both acceptance and resistance: pedagogy, affordance of modeling (tasks), modeling actions, and adjusting modeling. In the category of pedagogy, PTs displayed acceptance based on potential pedagogical benefits and resistance due to various concerns. The affordance of modeling (tasks) category emerged from instances when PTs showed acceptance or resistance while discussing the nature and quality of modeling tasks, often debating whether modeling is considered mathematics. PTs demonstrated both acceptance and resistance in their modeling actions, engaging in modeling cycles as students and designing/implementing MEAs as teachers. The adjusting modeling category captured instances where PTs accepted or resisted maintaining the qualities and nature of the modeling experience or converted modeling into a typical structured mathematics experience for students. While PTs displayed a mix of acceptance and resistance in their modeling actions, limitations were observed in embracing complexity and adhering to model principles. The study provides valuable insights into the challenges and opportunities of integrating mathematical modeling into teacher education, emphasizing the importance of addressing pedagogical concerns and providing support for effective implementation. In conclusion, this research offers a comprehensive understanding of PTs' engagement with modeling, advocating for a more focused discussion on the distinct nature and significance of mathematical modeling in the broader curriculum to establish a foundation for effective teacher education programs.Keywords: mathematical modeling, model eliciting activities, modeling pedagogy, secondary teacher education
Procedia PDF Downloads 6588 Unpacking the Rise of Social Entrepreneurship over Sustainable Entrepreneurship among Sri Lankan Exporters in SMEs Sector: A Case Study in Sri Lanka
Authors: Amarasinghe Shashikala, Pramudika Hansini, Fernando Tajan, Rathnayake Piyumi
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This study investigates the prominence of the social entrepreneurship (SE) model over the sustainable entrepreneurship model among Sri Lankan exporters in the small and medium enterprise (SME) sector. The primary objective of this study is to explore how the unique socio-economic contextual nuances of the country influence this behavior. The study employs a multiple-case study approach, collecting data from thirteen SEs in the SME sector. The findings reveal a significant alignment between SE and the lifestyle of the people in Sri Lanka, attributed largely to its deep-rooted religious setting and cultural norms. A crucial factor driving the prominence of SE is the predominantly labor-intensive nature of production processes within the exporters of the SME sector. These processes inherently lend themselves to SE, providing employment opportunities and fostering community engagement. Further, SE initiatives substantially resonate with community-centric practices, making them more appealing and accessible to the local populace. In contrast, the findings highlight a dilemma between cost-effectiveness and sustainable entrepreneurship. Transitioning to sustainable export products and production processes is demanded by foreign buyers and acknowledged as essential for environmental stewardship, which often requires capital-intensive makeovers. This investment inevitably raises the overall cost of the export product, making it less competitive in the global market. Interestingly, the study notes a disparity between international demand for sustainable products and the willingness of buyers to pay a premium for them. Despite the growing global preference for eco-friendly options, the findings suggest that the additional costs associated with sustainable entrepreneurship are not adequately reflected in the purchasing behavior of international buyers. The abundance of natural resources coupled with a minimal occurrence of natural catastrophes renders exporters less environmentally sensitive. The absence of robust policy support for environmental preservation exacerbates this inclination. Consequently, exporters exhibit a diminished motivation to incorporate environmental sustainability into their business decisions. Instead, attention is redirected towards factors such as the local population's minimum standards of living, prevalent social issues, governmental corruption and inefficiency, and rural poverty. These elements impel exporters to prioritize social well-being when making business decisions. Notably, the emphasis on social impact, rather than environmental impact, appears to be a generational trend, perpetuating a focus on societal aspects in the realm of business. In conclusion, the manifestation of entrepreneurial behavior within developing nations is notably contingent upon contextual nuances. This investigation contributes to a deeper understanding of the dynamics shaping the prevalence of SE over sustainable entrepreneurship among Sri Lankan exporters in the SME sector. The insights generated have implications for policymakers, industry stakeholders, and academics seeking to navigate the delicate balance between socio-cultural values, economic feasibility, and environmental sustainability in the pursuit of responsible business practices within the export sector.Keywords: small and medium enterprises, social entrepreneurship, Sri Lanka, sustainable entrepreneurship
Procedia PDF Downloads 7387 Exploring the Dose-Response Association of Lifestyle Behaviors and Mental Health among High School Students in the US: A Secondary Analysis of 2021 Adolescent Behaviors and Experiences Survey Data
Authors: Layla Haidar, Shari Esquenazi-Karonika
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Introduction: Mental health includes one’s emotional, psychological, and interpersonal well-being; it ranges from “good” to “poor” on a continuum. At the individual-level, it affects how a person thinks, feels, and acts. Moreover, it determines how they cope with stress, relate to others, and interface with their surroundings. Research has yielded that mental health is directly related with short- and long-term physical health (including chronic disease), health risk behaviors, education-level, employment, and social relationships. As is the case with physical conditions like diabetes, heart disease, and cancer, mitigating the behavioral and genetic risks of debilitating mental health conditions like anxiety and depression can nurture a healthier quality of mental health throughout one’s life. In order to maximize the benefits of prevention, it is important to identify modifiable risks and develop protective habits earlier in life. Methods: The Adolescent Behaviors and Experiences Survey (ABES) dataset was used for this study. The ABES survey was administered to high school students (9th-12th grade) during January 2021- June 2021 by the Centers for Disease Control and Prevention (CDC). The data was analyzed to identify any associations between feelings of sadness, hopelessness, or increased suicidality among high school students with relation to their participation on one or more sports teams and their average daily consumed screen time. Data was analyzed using descriptive and multivariable analytic techniques. A multinomial logistic regression of each variable was conducted to examine if there was an association, while controlling for grade-level, sex, and race. Results: The findings from this study are insightful for administrators and policymakers who wish to address mounting concerns related to student mental health. The study revealed that compared to a student who participated on zero sports teams, students who participated in 1 or more sports teams showed a significantly increased risk of depression (p<0.05). Conversely, the rate of depression in students was significantly less in those who consumed 5 or more hours of screen time per day, compared to those who consumed less than 1 hour per day of screen time (p<0.05). Conclusion: These findings are informative and highlight the importance of understanding the nuances of student participation on sports teams (e.g., physical exertion, social dynamics of team, and the level of competitiveness within the sport). Likewise, the context of an individual’s screen time (e.g., social media, engaging in team-based video games, or watching television) can inform parental or school-based policies about screen time activity. Although physical activity has been proven to be important for emotional and physical well-being of youth, playing on multiple teams could have negative consequences on the emotional state of high school students potentially due to fatigue, overtraining, and injuries. Existing literature has highlighted the negative effects of screen time; however, further research needs to consider the type of screen-based consumption to better understand its effects on mental health.Keywords: behavioral science, mental health, adolescents, prevention
Procedia PDF Downloads 10586 Essential Oils of Polygonum L. Plants Growing in Kazakhstan and Their Antibacterial and Antifungal Activity
Authors: Dmitry Yu. Korulkin, Raissa A. Muzychkina
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Bioactive substances of plant origin can be one of the advanced means of solution to the issue of combined therapy to inflammation. The main advantages of medical plants are softness and width of their therapeutic effect on an organism, the absence of side effects and complications even if the used continuously, high tolerability by patients. Moreover, medial plants are often the only and (or) cost-effective sources of natural biologically active substances and medicines. Along with other biologically active groups of chemical compounds, essential oils with wide range of pharmacological effects became very ingrained in medical practice. Essential oil was obtained by the method hydrodistillation air-dry aerial part of Polygonum L. plants using Clevenger apparatus. Qualitative composition of essential oils was analyzed by chromatography-mass-spectrometry method using Agilent 6890N apparatus. The qualitative analysis is based on the comparison of retention time and full mass-spectra with respective data on components of reference oils and pure compounds, if there were any, and with the data of libraries of mass-spectra Wiley 7th edition and NIST 02. The main components of essential oil are for: Polygonum amphibium L. - γ-terpinene, borneol, piperitol, 1,8-cyneole, α-pinene, linalool, terpinolene and sabinene; Polygonum minus Huds. Fl. Angl. – linalool, terpinolene, camphene, borneol, 1,8-cyneole, α-pinene, 4-terpineol and 1-octen-3-ol; Polygonum alpinum All. – camphene, sabinene, 1-octen-3-ol, 4-carene, p- and o-cymol, γ-terpinene, borneol, -terpineol; Polygonum persicaria L. - α-pinene, sabinene, -terpinene, 4-carene, 1,8-cyneole, borneol, 4-terpineol. Antibacterial activity was researched relating to strains of gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, Streptococcus agalacticae, relating to gram-negative strain Escherichia coli and to yeast fungus Сandida albicans using agar diffusion method. The medicines of comparison were gentamicin for bacteria and nystatin for yeast fungus Сandida albicans. It has been shown that Polygonum L. essential oils has moderate antibacterial effect to gram-positive microorganisms and weak antifungal activity to Candida albicans yeast fungus. At the second stage of our researches wound healing properties of ointment form of 3% essential oil was researched on the model of flat dermal wounds. To assess the influence of essential oil on healing processes the model of flat dermal wound. The speed of wound healing on rats of different groups was judged based on assessment the area of a wound from time to time. During research of wound healing properties disturbance of integral in neither group: general condition and behavior of animals, food intake, and excretion. Wound healing action of 3% ointment on base of Polygonum L. essential oil and polyethyleneglycol is comparable with the action of reference substances. As more favorable healing dynamics was observed in the experimental group than in control group, the tested ointment can be deemed more promising for further detailed study as wound healing means.Keywords: antibacterial, antifungal, bioactive substances, essential oils, isolation, Polygonum L.
Procedia PDF Downloads 53285 Rebuilding Beyond Bricks: The Environmental Psychological Foundations of Community Healing After the Lytton Creek Fire
Authors: Tugba Altin
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In a time characterized by escalating climate change impacts, communities globally face extreme events with deep-reaching tangible and intangible consequences. At the intersection of these phenomena lies the profound impact on the cultural and emotional connections that individuals forge with their environments. This study casts a spotlight on the Lytton Creek Fire of 2021, showcasing it as an exemplar of both the visible destruction brought by such events and the more covert yet deeply impactful disturbances to place attachment (PA). Defined as the emotional and cognitive bond individuals form with their surroundings, PA is critical in comprehending how such catastrophic events reshape cultural identity and the bond with the land. Against the stark backdrop of the Lytton Creek Fire's devastation, the research seeks to unpack the multilayered dynamics of PA amidst the tangible wreckage and the intangible repercussions such as emotional distress and disrupted cultural landscapes. Delving deeper, it examines how affected populations renegotiate their affiliations with these drastically altered environments, grappling with both the tangible loss of their homes and the intangible challenges to solace, identity, and community cohesion. This exploration is instrumental in the broader climate change narrative, as it offers crucial insights into how these personal-place relationships can influence and shape climate adaptation and recovery strategies. Departing from traditional data collection methodologies, this study adopts an interpretive phenomenological approach enriched by hermeneutic insights and places the experiences of the Lytton community and its co-researchers at its core. Instead of conventional interviews, innovative methods like walking audio sessions and photo elicitation are employed. These techniques allow participants to immerse themselves back into the environment, reviving and voicing their memories and emotions in real-time. Walking audio captures reflections on spatial narratives after the trauma, whereas photo voices encapsulate the intangible emotions, presenting a visual representation of place-based experiences. Key findings emphasize the indispensability of addressing both the tangible and intangible traumas in community recovery efforts post-disaster. The profound changes to the cultural landscape and the subsequent shifts in PA underscore the need for holistic, culturally attuned, and emotionally insightful adaptation strategies. These strategies, rooted in the lived experiences and testimonies of the affected individuals, promise more resonant and effective recovery efforts. The research further contributes to climate change discourse, highlighting the intertwined pathways of tangible reconstruction and the essentiality of emotional and cultural rejuvenation. Furthermore, the use of participatory methodologies in this inquiry challenges traditional research paradigms, pointing to potential evolutionary shifts in qualitative research norms. Ultimately, this study underscores the need for a more integrative approach in addressing the aftermath of environmental disasters, ensuring that both physical and emotional rebuilding are given equal emphasis.Keywords: place attachment, community recovery, disaster reponse, sensory responses, intangible traumas, visual methodologies
Procedia PDF Downloads 6284 Allylation of Active Methylene Compounds with Cyclic Baylis-Hillman Alcohols: Why Is It Direct and Not Conjugate?
Authors: Karim Hrratha, Khaled Essalahb, Christophe Morellc, Henry Chermettec, Salima Boughdiria
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Among the carbon-carbon bond formation types, allylation of active methylene compounds with cyclic Baylis-Hillman (BH) alcohols is a reliable and widely used method. This reaction is a very attractive tool in organic synthesis of biological and biodiesel compounds. Thus, in view of an insistent and peremptory request for an efficient and straightly method for synthesizing the desired product, a thorough analysis of various aspects of the reaction processes is an important task. The product afforded by the reaction of active methylene with BH alcohols depends largely on the experimental conditions, notably on the catalyst properties. All experiments reported that catalysis is needed for this reaction type because of the poor ability of alcohol hydroxyl group to be as a suitable leaving group. Within the catalysts, several transition- metal based have been used such as palladium in the presence of acid or base and have been considered as reliable methods. Furthemore, acid catalysts such as BF3.OEt2, BiX3 (X= Cl, Br, I, (OTf)3), InCl3, Yb(OTf)3, FeCl3, p-TsOH and H-montmorillonite have been employed to activate the C-C bond formation through the alkylation of active methylene compounds. Interestingly a report of a smoothly process for the ability of 4-imethyaminopyridine(DMAP) to catalyze the allylation reaction of active methylene compounds with cyclic Baylis-Hillman (BH) alcohol appeared recently. However, the reaction mechanism remains ambiguous, since the C- allylation process leads to an unexpected product (noted P1), corresponding to a direct allylation instead of conjugate allylation, which involves the most electrophilic center according to the electron withdrawing group CO effect. The main objective of the present theoretical study is to better understand the role of the DMAP catalytic activity as well as the process leading to the end- product (P1) for the catalytic reaction of a cyclic BH alcohol with active methylene compounds. For that purpose, we have carried out computations of a set of active methylene compounds varying by R1 and R2 toward the same alcohol, and we have attempted to rationalize the mechanisms thanks to the acid–base approach, and conceptual DFT tools such as chemical potential, hardness, Fukui functions, electrophilicity index and dual descriptor, as these approaches have shown a good prediction of reactions products.The present work is then organized as follows: In a first part some computational details will be given, introducing the reactivity indexes used in the present work, then Section 3 is dedicated to the discussion of the prediction of the selectivity and regioselectivity. The paper ends with some concluding remarks. In this work, we have shown, through DFT method at the B3LYP/6-311++G(d,p) level of theory that: The allylation of active methylene compounds with cyclic BH alcohol is governed by orbital control character. Hence the end- product denoted P1 is generated by direct allylation.Keywords: DFT calculation, gas phase pKa, theoretical mechanism, orbital control, charge control, Fukui function, transition state
Procedia PDF Downloads 30683 Modeling and Design of a Solar Thermal Open Volumetric Air Receiver
Authors: Piyush Sharma, Laltu Chandra, P. S. Ghoshdastidar, Rajiv Shekhar
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Metals processing operations such as melting and heat treatment of metals are energy-intensive, requiring temperatures greater than 500oC. The desired temperature in these industrial furnaces is attained by circulating electrically-heated air. In most of these furnaces, electricity produced from captive coal-based thermal power plants is used. Solar thermal energy could be a viable heat source in these furnaces. A retrofitted solar convective furnace (SCF) concept, which uses solar thermal generated hot air, has been proposed. Critical to the success of a SCF is the design of an open volumetric air receiver (OVAR), which can heat air in excess of 800oC. The OVAR is placed on top of a tower and receives concentrated solar radiation from a heliostat field. Absorbers, mixer assembly, and the return air flow chamber (RAFC) are the major components of an OVAR. The absorber is a porous structure that transfers heat from concentrated solar radiation to ambient air, referred to as primary air. The mixer ensures uniform air temperature at the receiver exit. Flow of the relatively cooler return air in the RAFC ensures that the absorbers do not fail by overheating. In an earlier publication, the detailed design basis, fabrication, and characterization of a 2 kWth open volumetric air receiver (OVAR) based laboratory solar air tower simulator was presented. Development of an experimentally-validated, CFD based mathematical model which can ultimately be used for the design and scale-up of an OVAR has been the major objective of this investigation. In contrast to the published literature, where flow and heat transfer have been modeled primarily in a single absorber module, the present study has modeled the entire receiver assembly, including the RAFC. Flow and heat transfer calculations have been carried out in ANSYS using the LTNE model. The complex return air flow pattern in the RAFC requires complicated meshes and is computational and time intensive. Hence a simple, realistic 1-D mathematical model, which circumvents the need for carrying out detailed flow and heat transfer calculations, has also been proposed. Several important results have emerged from this investigation. Circumferential electrical heating of absorbers can mimic frontal heating by concentrated solar radiation reasonably well in testing and characterizing the performance of an OVAR. Circumferential heating, therefore, obviates the need for expensive high solar concentration simulators. Predictions suggest that the ratio of power on aperture (POA) and mass flow rate of air (MFR) is a normalizing parameter for characterizing the thermal performance of an OVAR. Increasing POA/MFR increases the maximum temperature of air, but decreases the thermal efficiency of an OVAR. Predictions of the 1-D mathematical are within 5% of ANSYS predictions and computation time is reduced from ~ 5 hours to a few seconds.Keywords: absorbers, mixer assembly, open volumetric air receiver, return air flow chamber, solar thermal energy
Procedia PDF Downloads 19782 Complete Genome Sequence Analysis of Pasteurella multocida Subspecies multocida Serotype A Strain PMTB2.1
Authors: Shagufta Jabeen, Faez J. Firdaus Abdullah, Zunita Zakaria, Nurulfiza M. Isa, Yung C. Tan, Wai Y. Yee, Abdul R. Omar
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Pasteurella multocida (PM) is an important veterinary opportunistic pathogen particularly associated with septicemic pasteurellosis, pneumonic pasteurellosis and hemorrhagic septicemia in cattle and buffaloes. P. multocida serotype A has been reported to cause fatal pneumonia and septicemia. Pasteurella multocida subspecies multocida of serotype A Malaysian isolate PMTB2.1 was first isolated from buffaloes died of septicemia. In this study, the genome of P. multocida strain PMTB2.1 was sequenced using third-generation sequencing technology, PacBio RS2 system and analyzed bioinformatically via de novo analysis followed by in-depth analysis based on comparative genomics. Bioinformatics analysis based on de novo assembly of PacBio raw reads generated 3 contigs followed by gap filling of aligned contigs with PCR sequencing, generated a single contiguous circular chromosome with a genomic size of 2,315,138 bp and a GC content of approximately 40.32% (Accession number CP007205). The PMTB2.1 genome comprised of 2,176 protein-coding sequences, 6 rRNA operons and 56 tRNA and 4 ncRNAs sequences. The comparative genome sequence analysis of PMTB2.1 with nine complete genomes which include Actinobacillus pleuropneumoniae, Haemophilus parasuis, Escherichia coli and five P. multocida complete genome sequences including, PM70, PM36950, PMHN06, PM3480, PMHB01 and PMTB2.1 was carried out based on OrthoMCL analysis and Venn diagram. The analysis showed that 282 CDs (13%) are unique to PMTB2.1and 1,125 CDs with orthologs in all. This reflects overall close relationship of these bacteria and supports the classification in the Gamma subdivision of the Proteobacteria. In addition, genomic distance analysis among all nine genomes indicated that PMTB2.1 is closely related with other five Pasteurella species with genomic distance less than 0.13. Synteny analysis shows subtle differences in genetic structures among different P.multocida indicating the dynamics of frequent gene transfer events among different P. multocida strains. However, PM3480 and PM70 exhibited exceptionally large structural variation since they were swine and chicken isolates. Furthermore, genomic structure of PMTB2.1 is more resembling that of PM36950 with a genomic size difference of approximately 34,380 kb (smaller than PM36950) and strain-specific Integrative and Conjugative Elements (ICE) which was found only in PM36950 is absent in PMTB2.1. Meanwhile, two intact prophages sequences of approximately 62 kb were found to be present only in PMTB2.1. One of phage is similar to transposable phage SfMu. The phylogenomic tree was constructed and rooted with E. coli, A. pleuropneumoniae and H. parasuis based on OrthoMCL analysis. The genomes of P. multocida strain PMTB2.1 were clustered with bovine isolates of P. multocida strain PM36950 and PMHB01 and were separated from avian isolate PM70 and swine isolates PM3480 and PMHN06 and are distant from Actinobacillus and Haemophilus. Previous studies based on Single Nucleotide Polymorphism (SNPs) and Multilocus Sequence Typing (MLST) unable to show a clear phylogenetic relatedness between Pasteurella multocida and the different host. In conclusion, this study has provided insight on the genomic structure of PMTB2.1 in terms of potential genes that can function as virulence factors for future study in elucidating the mechanisms behind the ability of the bacteria in causing diseases in susceptible animals.Keywords: comparative genomics, DNA sequencing, phage, phylogenomics
Procedia PDF Downloads 18881 Dynamic Facades: A Literature Review on Double-Skin Façade with Lightweight Materials
Authors: Victor Mantilla, Romeu Vicente, António Figueiredo, Victor Ferreira, Sandra Sorte
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Integrating dynamic facades into contemporary building design is shaping a new era of energy efficiency and user comfort. These innovative facades, often constructed using lightweight construction systems and materials, offer an opportunity to have a responsive and adaptive nature to the dynamic behavior of the outdoor climate. Therefore, in regions characterized by high fluctuations in daily temperatures, the ability to adapt to environmental changes is of paramount importance and a challenge. This paper presents a thorough review of the state of the art on double-skin facades (DSF), focusing on lightweight solutions for the external envelope. Dynamic facades featuring elements like movable shading devices, phase change materials, and advanced control systems have revolutionized the built environment. They offer a promising path for reducing energy consumption while enhancing occupant well-being. Lightweight construction systems are increasingly becoming the choice for the constitution of these facade solutions, offering benefits such as reduced structural loads and reduced construction waste, improving overall sustainability. However, the performance of dynamic facades based on low thermal inertia solutions in climatic contexts with high thermal amplitude is still in need of research since their ability to adapt is traduced in variability/manipulation of the thermal transmittance coefficient (U-value). Emerging technologies can enable such a dynamic thermal behavior through innovative materials, changes in geometry and control to optimize the facade performance. These innovations will allow a facade system to respond to shifting outdoor temperature, relative humidity, wind, and solar radiation conditions, ensuring that energy efficiency and occupant comfort are both met/coupled. This review addresses the potential configuration of double-skin facades, particularly concerning their responsiveness to seasonal variations in temperature, with a specific focus on addressing the challenges posed by winter and summer conditions. Notably, the design of a dynamic facade is significantly shaped by several pivotal factors, including the choice of materials, geometric considerations, and the implementation of effective monitoring systems. Within the realm of double skin facades, various configurations are explored, encompassing exhaust air, supply air, and thermal buffering mechanisms. According to the review places a specific emphasis on the thermal dynamics at play, closely examining the impact of factors such as the color of the facade, the slat angle's dimensions, and the positioning and type of shading devices employed in these innovative architectural structures.This paper will synthesize the current research trends in this field, with the presentation of case studies and technological innovations with a comprehensive understanding of the cutting-edge solutions propelling the evolution of building envelopes in the face of climate change, namely focusing on double-skin lightweight solutions to create sustainable, adaptable, and responsive building envelopes. As indicated in the review, flexible and lightweight systems have broad applicability across all building sectors, and there is a growing recognition that retrofitting existing buildings may emerge as the predominant approach.Keywords: adaptive, control systems, dynamic facades, energy efficiency, responsive, thermal comfort, thermal transmittance
Procedia PDF Downloads 8080 Deciphering Information Quality: Unraveling the Impact of Information Distortion in the UK Aerospace Supply Chains
Authors: Jing Jin
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The incorporation of artificial intelligence (AI) and machine learning (ML) in aircraft manufacturing and aerospace supply chains leads to the generation of a substantial amount of data among various tiers of suppliers and OEMs. Identifying the high-quality information challenges decision-makers. The application of AI/ML models necessitates access to 'high-quality' information to yield desired outputs. However, the process of information sharing introduces complexities, including distortion through various communication channels and biases introduced by both human and AI entities. This phenomenon significantly influences the quality of information, impacting decision-makers engaged in configuring supply chain systems. Traditionally, distorted information is categorized as 'low-quality'; however, this study challenges this perception, positing that distorted information, contributing to stakeholder goals, can be deemed high-quality within supply chains. The main aim of this study is to identify and evaluate the dimensions of information quality crucial to the UK aerospace supply chain. Guided by a central research question, "What information quality dimensions are considered when defining information quality in the UK aerospace supply chain?" the study delves into the intricate dynamics of information quality in the aerospace industry. Additionally, the research explores the nuanced impact of information distortion on stakeholders' decision-making processes, addressing the question, "How does the information distortion phenomenon influence stakeholders’ decisions regarding information quality in the UK aerospace supply chain system?" This study employs deductive methodologies rooted in positivism, utilizing a cross-sectional approach and a mono-quantitative method -a questionnaire survey. Data is systematically collected from diverse tiers of supply chain stakeholders, encompassing end-customers, OEMs, Tier 0.5, Tier 1, and Tier 2 suppliers. Employing robust statistical data analysis methods, including mean values, mode values, standard deviation, one-way analysis of variance (ANOVA), and Pearson’s correlation analysis, the study interprets and extracts meaningful insights from the gathered data. Initial analyses challenge conventional notions, revealing that information distortion positively influences the definition of information quality, disrupting the established perception of distorted information as inherently low-quality. Further exploration through correlation analysis unveils the varied perspectives of different stakeholder tiers on the impact of information distortion on specific information quality dimensions. For instance, Tier 2 suppliers demonstrate strong positive correlations between information distortion and dimensions like access security, accuracy, interpretability, and timeliness. Conversely, Tier 1 suppliers emphasise strong negative influences on the security of accessing information and negligible impact on information timeliness. Tier 0.5 suppliers showcase very strong positive correlations with dimensions like conciseness and completeness, while OEMs exhibit limited interest in considering information distortion within the supply chain. Introducing social network analysis (SNA) provides a structural understanding of the relationships between information distortion and quality dimensions. The moderately high density of ‘information distortion-by-information quality’ underscores the interconnected nature of these factors. In conclusion, this study offers a nuanced exploration of information quality dimensions in the UK aerospace supply chain, highlighting the significance of individual perspectives across different tiers. The positive influence of information distortion challenges prevailing assumptions, fostering a more nuanced understanding of information's role in the Industry 4.0 landscape.Keywords: information distortion, information quality, supply chain configuration, UK aerospace industry
Procedia PDF Downloads 6479 Single Cell Rna Sequencing Operating from Benchside to Bedside: An Interesting Entry into Translational Genomics
Authors: Leo Nnamdi Ozurumba-Dwight
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Single-cell genomic analytical systems have proved to be a platform to isolate bulk cells into selected single cells for genomic, proteomic, and related metabolomic studies. This is enabling systematic investigations of the level of heterogeneity in a diverse and wide pool of cell populations. Single cell technologies, embracing techniques such as high parameter flow cytometry, single-cell sequencing, and high-resolution images are playing vital roles in these investigations on messenger ribonucleic acid (mRNA) molecules and related gene expressions in tracking the nature and course of disease conditions. This entails targeted molecular investigations on unit cells that help us understand cell behavoiur and expressions, which can be examined for their health implications on the health state of patients. One of the vital good sides of single-cell RNA sequencing (scRNA seq) is its probing capacity to detect deranged or abnormal cell populations present within homogenously perceived pooled cells, which would have evaded cursory screening on the pooled cell populations of biological samples obtained as part of diagnostic procedures. Despite conduction of just single-cell transcriptome analysis, scRNAseq now permits comparison of the transcriptome of the individual cells, which can be evaluated for gene expressional patterns that depict areas of heterogeneity with pharmaceutical drug discovery and clinical treatment applications. It is vital to strictly work through the tools of investigations from wet lab to bioinformatics and computational tooled analyses. In the precise steps for scRNAseq, it is critical to do thorough and effective isolation of viable single cells from the tissues of interest using dependable techniques (such as FACS) before proceeding to lysis, as this enhances the appropriate picking of quality mRNA molecules for subsequent sequencing (such as by the use of Polymerase Chain Reaction machine). Interestingly, scRNAseq can be deployed to analyze various types of biological samples such as embryos, nervous systems, tumour cells, stem cells, lymphocytes, and haematopoietic cells. In haematopoietic cells, it can be used to stratify acute myeloid leukemia patterns in patients, sorting them out into cohorts that enable re-modeling of treatment regimens based on stratified presentations. In immunotherapy, it can furnish specialist clinician-immunologist with tools to re-model treatment for each patient, an attribute of precision medicine. Finally, the good predictive attribute of scRNAseq can help reduce the cost of treatment for patients, thus attracting more patients who would have otherwise been discouraged from seeking quality clinical consultation help due to perceived high cost. This is a positive paradigm shift for patients’ attitudes primed towards seeking treatment.Keywords: immunotherapy, transcriptome, re-modeling, mRNA, scRNA-seq
Procedia PDF Downloads 17678 Regulatory and Economic Challenges of AI Integration in Cyber Insurance
Authors: Shreyas Kumar, Mili Shangari
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Integrating artificial intelligence (AI) in the cyber insurance sector represents a significant advancement, offering the potential to revolutionize risk assessment, fraud detection, and claims processing. However, this integration introduces a range of regulatory and economic challenges that must be addressed to ensure responsible and effective deployment of AI technologies. This paper examines the multifaceted regulatory landscape governing AI in cyber insurance and explores the economic implications of compliance, innovation, and market dynamics. AI's capabilities in processing vast amounts of data and identifying patterns make it an invaluable tool for insurers in managing cyber risks. Yet, the application of AI in this domain is subject to stringent regulatory scrutiny aimed at safeguarding data privacy, ensuring algorithmic transparency, and preventing biases. Regulatory bodies, such as the European Union with its General Data Protection Regulation (GDPR), mandate strict compliance requirements that can significantly impact the deployment of AI systems. These regulations necessitate robust data protection measures, ethical AI practices, and clear accountability frameworks, all of which entail substantial compliance costs for insurers. The economic implications of these regulatory requirements are profound. Insurers must invest heavily in upgrading their IT infrastructure, implementing robust data governance frameworks, and training personnel to handle AI systems ethically and effectively. These investments, while essential for regulatory compliance, can strain financial resources, particularly for smaller insurers, potentially leading to market consolidation. Furthermore, the cost of regulatory compliance can translate into higher premiums for policyholders, affecting the overall affordability and accessibility of cyber insurance. Despite these challenges, the potential economic benefits of AI integration in cyber insurance are significant. AI-enhanced risk assessment models can provide more accurate pricing, reduce the incidence of fraudulent claims, and expedite claims processing, leading to overall cost savings and increased efficiency. These efficiencies can improve the competitiveness of insurers and drive innovation in product offerings. However, balancing these benefits with regulatory compliance is crucial to avoid legal penalties and reputational damage. The paper also explores the potential risks associated with AI integration, such as algorithmic biases that could lead to unfair discrimination in policy underwriting and claims adjudication. Regulatory frameworks need to evolve to address these issues, promoting fairness and transparency in AI applications. Policymakers play a critical role in creating a balanced regulatory environment that fosters innovation while protecting consumer rights and ensuring market stability. In conclusion, the integration of AI in cyber insurance presents both regulatory and economic challenges that require a coordinated approach involving regulators, insurers, and other stakeholders. By navigating these challenges effectively, the industry can harness the transformative potential of AI, driving advancements in risk management and enhancing the resilience of the cyber insurance market. This paper provides insights and recommendations for policymakers and industry leaders to achieve a balanced and sustainable integration of AI technologies in cyber insurance.Keywords: artificial intelligence (AI), cyber insurance, regulatory compliance, economic impact, risk assessment, fraud detection, cyber liability insurance, risk management, ransomware
Procedia PDF Downloads 3377 Modeling Driving Distraction Considering Psychological-Physical Constraints
Authors: Yixin Zhu, Lishengsa Yue, Jian Sun, Lanyue Tang
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Modeling driving distraction in microscopic traffic simulation is crucial for enhancing simulation accuracy. Current driving distraction models are mainly derived from physical motion constraints under distracted states, in which distraction-related error terms are added to existing microscopic driver models. However, the model accuracy is not very satisfying, due to a lack of modeling the cognitive mechanism underlying the distraction. This study models driving distraction based on the Queueing Network Human Processor model (QN-MHP). This study utilizes the queuing structure of the model to perform task invocation and switching for distracted operation and control of the vehicle under driver distraction. Based on the assumption of the QN-MHP model about the cognitive sub-network, server F is a structural bottleneck. The latter information must wait for the previous information to leave server F before it can be processed in server F. Therefore, the waiting time for task switching needs to be calculated. Since the QN-MHP model has different information processing paths for auditory information and visual information, this study divides driving distraction into two types: auditory distraction and visual distraction. For visual distraction, both the visual distraction task and the driving task need to go through the visual perception sub-network, and the stimuli of the two are asynchronous, which is called stimulus on asynchrony (SOA), so when calculating the waiting time for switching tasks, it is necessary to consider it. In the case of auditory distraction, the auditory distraction task and the driving task do not need to compete for the server resources of the perceptual sub-network, and their stimuli can be synchronized without considering the time difference in receiving the stimuli. According to the Theory of Planned Behavior for drivers (TPB), this study uses risk entropy as the decision criterion for driver task switching. A logistic regression model is used with risk entropy as the independent variable to determine whether the driver performs a distraction task, to explain the relationship between perceived risk and distraction. Furthermore, to model a driver’s perception characteristics, a neurophysiological model of visual distraction tasks is incorporated into the QN-MHP, and executes the classical Intelligent Driver Model. The proposed driving distraction model integrates the psychological cognitive process of a driver with the physical motion characteristics, resulting in both high accuracy and interpretability. This paper uses 773 segments of distracted car-following in Shanghai Naturalistic Driving Study data (SH-NDS) to classify the patterns of distracted behavior on different road facilities and obtains three types of distraction patterns: numbness, delay, and aggressiveness. The model was calibrated and verified by simulation. The results indicate that the model can effectively simulate the distracted car-following behavior of different patterns on various roadway facilities, and its performance is better than the traditional IDM model with distraction-related error terms. The proposed model overcomes the limitations of physical-constraints-based models in replicating dangerous driving behaviors, and internal characteristics of an individual. Moreover, the model is demonstrated to effectively generate more dangerous distracted driving scenarios, which can be used to construct high-value automated driving test scenarios.Keywords: computational cognitive model, driving distraction, microscopic traffic simulation, psychological-physical constraints
Procedia PDF Downloads 9176 Reactive X Proactive Searches on Internet After Leprosy Institutional Campaigns in Brazil: A Google Trends Analysis
Authors: Paulo Roberto Vasconcellos-Silva
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The "Janeiro Roxo" (Purple January) campaign in Brazil aims to promote awareness of leprosy and its early symptoms. The COVID-19 pandemic has adversely affected institutional campaigns, mostly considering leprosy a neglected disease by the media. Google Trends (GT) is a tool that tracks user searches on Google, providing insights into the popularity of specific search terms. Our prior research has categorized online searches into two types: "Reactive searches," driven by transient campaign-related stimuli, and "Proactive searches," driven by personal interest in early symptoms and self-diagnosis. Using GT we studied: (i) the impact of "Janeiro Roxo" on public interest in leprosy (assessed through reactive searches) and its early symptoms (evaluated through proactive searches) over the past five years; (ii) changes in public interest during and after the COVID-19 pandemic; (iii) patterns in the dynamics of reactive and proactive searches Methods: We used GT's "Relative Search Volume" (RSV) to gauge public interest on a scale from 0 to 100. "HANSENÍASE" (HAN) was a proxy for reactive searches, and "HANSENÍASE SINTOMAS" (leprosy symptoms) (H.SIN) for proactive searches (interest in leprosy or in self-diagnosis). We analyzed 261 weeks of data from 2018 to 2023, using polynomial trend lines to model trends over this period. Analysis of Variance (ANOVA) was used to compare weekly RSV, monthly (MM) and annual means (AM). Results: Over a span of 261 weeks, there was consistently higher Relative Search Volume (RSV) for HAN compared to H.SIN. Both search terms exhibited their highest (MM) in January months during all periods. COVID-19 pandemic: a decline was observed during the pandemic years (2020-2021). There was a 24% decrease in RSV for HAN and a 32.5% decrease for H.SIN. Both HAN and H.SIN regained their pre-pandemic search levels in January 2022-2023. Breakpoints indicated abrupt changes - in the 26th week (February 2019), 55th and 213th weeks (September 2019 and 2022) related to September regional campaigns (interrupted in 2020-2021). Trend lines for HAN exhibited an upward curve between 33rd-45th week (April to June 2019), a pandemic-related downward trend between 120th-136th week (December 2020 to March 2021), and an upward trend between 220th-240th week (November 2022 to March 2023). Conclusion: The "Janeiro Roxo" campaign, along with other media-driven activities, exerts a notable influence on both reactive and proactive searches related to leprosy topics. Reactive searches, driven by campaign stimuli, significantly outnumber proactive searches. Despite the interruption of the campaign due to the pandemic, there was a subsequent resurgence in both types of searches. The recovery observed in reactive and proactive searches post-campaign interruption underscores the effectiveness of such initiatives, particularly at the national level. This suggests that regional campaigns aimed at leprosy awareness can be considered highly successful in stimulating proactive public engagement. The evaluation of internet-based campaign programs proves valuable not only for assessing their impact but also for identifying the needs of vulnerable regions. These programs can play a crucial role in integrating regions and highlighting their needs for assistance services in the context of leprosy awareness.Keywords: health communication, leprosy, health campaigns, information seeking behavior, Google Trends, reactive searches, proactive searches, leprosy early identification
Procedia PDF Downloads 6175 Application of the Standard Deviation in Regulating Design Variation of Urban Solutions Generated through Evolutionary Computation
Authors: Mohammed Makki, Milad Showkatbakhsh, Aiman Tabony
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Computational applications of natural evolutionary processes as problem-solving tools have been well established since the mid-20th century. However, their application within architecture and design has only gained ground in recent years, with an increasing number of academics and professionals in the field electing to utilize evolutionary computation to address problems comprised from multiple conflicting objectives with no clear optimal solution. Recent advances in computer science and its consequent constructive influence on the architectural discourse has led to the emergence of multiple algorithmic processes capable of simulating the evolutionary process in nature within an efficient timescale. Many of the developed processes of generating a population of candidate solutions to a design problem through an evolutionary based stochastic search process are often driven through the application of both environmental and architectural parameters. These methods allow for conflicting objectives to be simultaneously, independently, and objectively optimized. This is an essential approach in design problems with a final product that must address the demand of a multitude of individuals with various requirements. However, one of the main challenges encountered through the application of an evolutionary process as a design tool is the ability for the simulation to maintain variation amongst design solutions in the population while simultaneously increasing in fitness. This is most commonly known as the ‘golden rule’ of balancing exploration and exploitation over time; the difficulty of achieving this balance in the simulation is due to the tendency of either variation or optimization being favored as the simulation progresses. In such cases, the generated population of candidate solutions has either optimized very early in the simulation, or has continued to maintain high levels of variation to which an optimal set could not be discerned; thus, providing the user with a solution set that has not evolved efficiently to the objectives outlined in the problem at hand. As such, the experiments presented in this paper seek to achieve the ‘golden rule’ by incorporating a mathematical fitness criterion for the development of an urban tissue comprised from the superblock as its primary architectural element. The mathematical value investigated in the experiments is the standard deviation factor. Traditionally, the standard deviation factor has been used as an analytical value rather than a generative one, conventionally used to measure the distribution of variation within a population by calculating the degree by which the majority of the population deviates from the mean. A higher standard deviation value delineates a higher number of the population is clustered around the mean and thus limited variation within the population, while a lower standard deviation value is due to greater variation within the population and a lack of convergence towards an optimal solution. The results presented will aim to clarify the extent to which the utilization of the standard deviation factor as a fitness criterion can be advantageous to generating fitter individuals in a more efficient timeframe when compared to conventional simulations that only incorporate architectural and environmental parameters.Keywords: architecture, computation, evolution, standard deviation, urban
Procedia PDF Downloads 13374 Smart Laboratory for Clean Rivers in India - An Indo-Danish Collaboration
Authors: Nikhilesh Singh, Shishir Gaur, Anitha K. Sharma
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Climate change and anthropogenic stress have severely affected ecosystems all over the globe. Indian rivers are under immense pressure, facing challenges like pollution, encroachment, extreme fluctuation in the flow regime, local ignorance and lack of coordination between stakeholders. To counter all these issues a holistic river rejuvenation plan is needed that tests, innovates and implements sustainable solutions in the river space for sustainable river management. Smart Laboratory for Clean Rivers (SLCR) an Indo-Danish collaboration project, provides a living lab setup that brings all the stakeholders (government agencies, academic and industrial partners and locals) together to engage, learn, co-creating and experiment for a clean and sustainable river that last for ages. Just like every mega project requires piloting, SLCR has opted for a small catchment of the Varuna River, located in the Middle Ganga Basin in India. Considering the integrated approach of river rejuvenation, SLCR embraces various techniques and upgrades for rejuvenation. Likely, maintaining flow in the channel in the lean period, Managed Aquifer Recharge (MAR) is a proven technology. In SLCR, Floa-TEM high-resolution lithological data is used in MAR models to have better decision-making for MAR structures nearby of the river to enhance the river aquifer exchanges. Furthermore, the concerns of quality in the river are a big issue. A city like Varanasi which is located in the last stretch of the river, generates almost 260 MLD of domestic waste in the catchment. The existing STP system is working at full efficiency. Instead of installing a new STP for the future, SLCR is upgrading those STPs with an IoT-based system that optimizes according to the nutrient load and energy consumption. SLCR also advocate nature-based solutions like a reed bed for the drains having less flow. In search of micropollutants, SLCR uses fingerprint analysis involves employing advanced techniques like chromatography and mass spectrometry to create unique chemical profiles. However, rejuvenation attempts cannot be possible without involving the entire catchment. A holistic water management plan that includes storm management, water harvesting structure to efficiently manage the flow of water in the catchment and installation of several buffer zones to restrict pollutants entering into the river. Similarly, carbon (emission and sequestration) is also an important parameter for the catchment. By adopting eco-friendly practices, a ripple effect positively influences the catchment's water dynamics and aids in the revival of river systems. SLCR has adopted 4 villages to make them carbon-neutral and water-positive. Moreover, for the 24×7 monitoring of the river and the catchment, robust IoT devices are going to be installed to observe, river and groundwater quality, groundwater level, river discharge and carbon emission in the catchment and ultimately provide fuel for the data analytics. In its completion, SLCR will provide a river restoration manual, which will strategise the detailed plan and way of implementation for stakeholders. Lastly, the entire process is planned in such a way that will be managed by local administrations and stakeholders equipped with capacity-building activity. This holistic approach makes SLCR unique in the field of river rejuvenation.Keywords: sustainable management, holistic approach, living lab, integrated river management
Procedia PDF Downloads 6073 Computer Based Identification of Possible Molecular Targets for Induction of Drug Resistance Reversion in Multidrug Resistant Mycobacterium Tuberculosis
Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin
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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis
Procedia PDF Downloads 26372 Computational and Experimental Study of the Mechanics of Heart Tube Formation in the Chick Embryo
Authors: Hadi S. Hosseini, Larry A. Taber
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In the embryo, heart is initially a simple tubular structure that undergoes complex morphological changes as it transforms into a four-chambered pump. This work focuses on mechanisms that create heart tube (HT). The early embryo is composed of three relatively flat primary germ layers called endoderm, mesoderm, and ectoderm. Precardiac cells located within bilateral regions of the mesoderm called heart fields (HFs) fold and fuse along the embryonic midline to create the HT. The right and left halves of this plate fold symmetrically to bring their upper edges into contact along the midline, where they fuse. In a region near the fusion line, these layers then separate to generate the primitive HT and foregut, which then extend vertically. The anterior intestinal portal (AIP) is the opening at the caudal end of the foregut, which descends as the HT lengthens. The biomechanical mechanisms that drive this folding are poorly understood. Our central hypothesis is that folding is caused by differences in growth between the endoderm and mesoderm while subsequent extension is driven by contraction along the AIP. The feasibility of this hypothesis is examined using experiments with chick embryos and finite-element modeling (FEM). Fertilized white Leghorn chicken eggs were incubated for approximately 22-33 hours until appropriate Hamburger and Hamilton stage (HH5 to HH9) was reached. To inhibit contraction, embryos were cultured in media containing blebbistatin (myosin II inhibitor) for 18h. Three-dimensional models were created using ABAQUS (D. S. Simulia). The initial geometry consists of a flat plate including two layers representing the mesoderm and endoderm. Tissue was considered as a nonlinear elastic material with growth and contraction (negative growth) simulated using a theory, in which the total deformation gradient is given by F=F^*.G, where G is growth tensor and F* is the elastic deformation gradient tensor. In embryos exposed to blebbistatin, initial folding and AIP descension occurred normally. However, after HFs partially fused to create the upper part of the HT, fusion, and AIP descension stopped, and the HT failed to grow longer. These results suggest that cytoskeletal contraction is required only for the later stages of HT formation. In the model, a larger biaxial growth rate in the mesoderm compared to the endoderm causes the bilayered plate to bend ventrally, as the upper edge moves toward the midline, where it 'fuses' with the other half . This folding creates the upper section of the HT, as well as the foregut pocket bordered by the AIP. After this phase completes by stage HH7, contraction along the arch-shaped AIP pulls the lower edge of the plate downward, stretching the two layers. Results given by model are in reasonable agreement with experimental data for the shape of HT, as well as patterns of stress and strain. In conclusion, results of our study support our hypothesis for the creation of the heart tube.Keywords: heart tube formation, FEM, chick embryo, biomechanics
Procedia PDF Downloads 29671 Destructive and Nondestructive Characterization of Advanced High Strength Steels DP1000/1200
Authors: Carla M. Machado, André A. Silva, Armando Bastos, Telmo G. Santos, J. Pamies Teixeira
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Advanced high-strength steels (AHSS) are increasingly being used in automotive components. The use of AHSS sheets plays an important role in reducing weight, as well as increasing the resistance to impact in vehicle components. However, the large-scale use of these sheets becomes more difficult due to the limitations during the forming process. Such limitations are due to the elastically driven change of shape of a metal sheet during unloading and following forming, known as the springback effect. As the magnitude of the springback tends to increase with the strength of the material, it is among the most worrisome problems in the use of AHSS steels. The prediction of strain hardening, especially under non-proportional loading conditions, is very limited due to the lack of constitutive models and mainly due to very limited experimental tests. It is very clear from the literature that in experimental terms there is not much work to evaluate deformation behavior under real conditions, which implies a very limited and scarce development of mathematical models for these conditions. The Bauschinger effect is also fundamental to the difference between kinematic and isotropic hardening models used to predict springback in sheet metal forming. It is of major importance to deepen the phenomenological knowledge of the mechanical and microstructural behavior of the materials, in order to be able to reproduce with high fidelity the behavior of extension of the materials by means of computational simulation. For this, a multi phenomenological analysis and characterization are necessary to understand the various aspects involved in plastic deformation, namely the stress-strain relations and also the variations of electrical conductivity and magnetic permeability associated with the metallurgical changes due to plastic deformation. Aiming a complete mechanical-microstructural characterization, uniaxial tensile tests involving successive cycles of loading and unloading were performed, as well as biaxial tests such as the Erichsen test. Also, nondestructive evaluation comprising eddy currents to verify microstructural changes due to plastic deformation and ultrasonic tests to evaluate the local variations of thickness were made. The material parameters for the stable yield function and the monotonic strain hardening were obtained using uniaxial tension tests in different material directions and balanced biaxial tests. Both the decrease of the modulus of elasticity and Bauschinger effect were determined through the load-unload tensile tests. By means of the eddy currents tests, it was possible to verify changes in the magnetic permeability of the material according to the different plastically deformed areas. The ultrasonic tests were an important aid to quantify the local plastic extension. With these data, it is possible to parameterize the different models of kinematic hardening to better approximate the results obtained by simulation with the experimental results, which are fundamental for the springback prediction of the stamped parts.Keywords: advanced high strength steel, Bauschinger effect, sheet metal forming, springback
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